Spleen-targeted delivery systems and strategies for spleen-related diseases.

The spleen, body's largest secondary lymphoid organ, is also a vital hematopoietic and immunological organ. It is regarded as one of the most significant organs in humans. As more researchers recognize the functions of the spleen, clinical methods for treating splenic diseases and spleen-targeted drug delivery systems to improve the efficacy of spleen-related therapies have gradually developed. Many modification strategies (size, charge, ligand, protein corona) and hitchhiking strategies (erythrocytes, neutrophils) of nanoparticles (NPs) have shown a significant increase in spleen targeting efficiency. However, most of the targeted drug therapy strategies for the spleen are to enhance or inhibit the immune function of the spleen to achieve therapeutic effects, and there are few studies on spleen-related diseases. In this review, we not only provide a detailed summary of the design rules for spleen-targeted drug delivery systems in recent years, but also introduce common spleen diseases (splenic tumors, splenic injuries, and splenomegaly) with the hopes of generating more ideas for future spleen research. The spleen consists of red pulp (RP), white pulp (WP), and marginal zone (MZ), and the anatomical structures of human and mouse spleen are different in the MZ, with bridging channels (BC) in the MZ of mouse. Spleen-targeted NPs can be modified in terms of size, charge, ligand, and protein corona, and the drug delivery system of erythrocyte and neutrophil hitchhiking also exists in spleen-targeted with significant delivery effects. Currently, there are two ways for a spleen-targeted drug delivery system to regulate the immune response of the spleen: on the one hand, to stimulate the spleen to produce more immune cells by enhancing the immune response, to kill the tumor cells and resist the growth of tumors, the indications of which include breast cancer, melanoma, and rectal cancer; on the other hand, to slow down the systemic or acute inflammatory diseases in the body by suppressing the immune response, such as rheumatoid arthritis. Currently, the development of medications that specifically target the spleen primarily relies on leveraging the immune capabilities of the spleen to treat disorders that are not directly related to the spleen. This is achieved by either increasing or suppressing the immune function of the spleen. Common splenic diseases include splenic tumors, splenic injury and splenomegaly. The figure was created with BioRender.com. [Display omitted] • Structure and function of the spleen contribute to targeted delivery • Strategies for designing spleen-targeted nanoparticles • Causes, signs and treatments of spleen-related diseases [ABSTRACT FROM AUTHOR]